1. Field of the Invention
The present invention is directed to pyrithione biocides, and more particularly to a stable, soluble biocidal composition displaying an enhanced biocidal effect, comprising an antimicrobially effective combination of pyrithione, pyrithione salt, or pyrithione adduct, a zinc source such a zinc alloy, zinc oxide, zinc hydroxide, or zinc salt, and 1,2-1,3 alkanolamines and 1,2-1,3-alkyldiamines. The biocidal composition is provided in the form of a biocidal composition concentrate that is suitably incorporated directly into a functional fluid (such as a metalworking fluid) or incorporated into a functional fluid “masterbatch”.
2. Brief Description of the Related Art
Polyvalent metal salts of pyrithione (also known as 1-hydroxy-2-pyridinethione; 2-pyridinethiol-1-oxide; 2-pyridinethione; 2-mercaptopyridine-N-oxide; pyridinethione; and pyridinethione-N-oxide) are known to be effective biocidal agents, and are widely used as fungicides and bacteriocides in paints and metalworking fluids. Pyrithiones are also used as fungicides and bacteriocides in personal care products such as anti-dandruff shampoos. The polyvalent metal salts of pyrithione are only sparingly soluble in water and include ferric pyrithione, ferrous pyrithione, aluminum pyrithione, bismuth pyrithione, strontium pyrithione, copper pyrithione, zinc pyrithione, cadmium pyrithione, and zirconium pyrithione. The most widely used divalent pyrithione salts are zinc pyrithione and copper pyrithione.
Zinc and copper pyrithione are useful as antimicrobial agents active against gram-positive and negative bacteria, fungi, and yeasts. Zinc pyrithione is used as an antidandruff component in shampoos, while technical suspensions of zinc pyrithione and/or copper pyrithione are used as preservatives in paints and polymers. Powders of these same salts are also used as cobiocides in antifouling paints. Synthesis of polyvalent pyrithione salts are described in U.S. Pat. No. 2,809,971 to Berstein et al. Other patents disclosing similar compounds and processes for making them include U.S. Pat. Nos. 2,786,847; 3,589,999; 3,590,035; 3,773,770.
While pyrithione biocides have proven useful for a wide range of applications as outlined above, the utility of these compounds is limited to the control of select species and strains of fungi and bacteria. Further, while higher concentrations of pyrithione or its salts have been observed to control the growth of a wider range of organisms, the useful amount of pyrithione or its salts that can be added to a commercial product is limited by efficacy and economic considerations, and, to a lesser extent, environmental and toxicological concerns.
Inorganic salts of zinc such as zinc chloride, zinc sulfate, and zinc oxide, have been employed as a bacteriostatic and/or fungistatic compounds in a large variety of products including paints, coatings, and antiseptics. However, while zinc salts are less toxic than pyrithione or its salts, these compounds do not possess the high biocidal efficacy that is desired in many commercial applications.
Certain combinations of pyrithione and zinc are known in the art. Illustratively, U.S. Pat. Nos. 5,854,266 and 5,883,154 disclose an aqueous antimicrobial composition protected against discoloration attributable to the presence of ferric ion or cupric ion therein, wherein the composition comprises pyrithione and a discoloration-inhibiting amount (between 0.001% to 10%) of a zinc compound selected from the group consisting of zinc salts of organic acids, zinc salts of inorganic acids, zinc hydroxide, zinc oxide, and combinations thereof. However, this patent does not describe any advantageous antimicrobial effects between pyrithione and zinc. Furthermore, at the concentrations employed in the patent, the compositions of pyrithione and zinc would not be soluble and thus could not be delivered together as a soluble biocidal composition. In another illustration, U.S. Pat. No. 4,161,526 discloses a white to cream yellow pyrithione salt or dipyrithione for application to skin or hair containing 0.01% to 1% of the zinc salt of an organic or inorganic acid, zinc hydroxide, zinc oxide, or combinations thereof. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt nor would it form a soluble composition of pyrithione and zinc.
While bacteria and fungi have presented microbial contamination problems for many years, biofilms have recently been appreciated as a significant new source of microbial contamination. Biofilms are generally characterized as aggregates of cells adhered to one another or to surfaces by an extracellular layer of slime. Biofilms are commonly found as contaminants in metalworking fluids because these fluids contain good carbon sources for growth of the organisms that are found in biofilms. However, high concentrations of biofilms in metalworking fluid result in rapid deterioration of the fluid, and can cause equipment problems and failure.
The growth of biofilms on surfaces can also enhance the rates of corrosion of metal surfaces and degradation of paints, surface coatings and the construction materials underlying these coatings. On ship hulls, the presence of biofilms can lead to increased drag and may encourage colonization by larger invertebrate biofouling organisms. Biofilms are often responsible for both internal and cutaneous infections. The increased resistance of biofilms to antimicrobial treatments often make biofilm-related infections more difficult to treat. Medical devices, such as cardiac implants and catheters, and medical instruments, such as dialysis machines and dental waterlines also become contaminated by biofilms and can spread infection.
While previous efforts have been made to control the growth and proliferation of biofilms, these efforts have met with only limited success. Research has indicated that biofilm cells are much more resistant to disinfection than free-living cells, due in large part to the extracellular slime layer which acts as a protective coating. Moreover, strategies to control microbial contamination heretofore were typically developed in the laboratory against free-living organisms, and little or no attention was given towards determining the effectiveness of antimicrobial agents against biofilm. Unfortunately, the resistant biofilms are generally not affected by previously employed antimicrobials. If not removed or destroyed, biofilms can cause a multitude of problems in functioning fluid applications, such as corrosion, clogging, slime build up on surfaces, foul odors, fluid instability, machine down-time, and the like.
Additional representative patents and publications showing the state of the art in the microbial disinfection area are as follows:
U.S. Pat. No. 4,654,213 discloses an antimicrobial composition in which a water-soluble salt of zinc enhances the activity of the MgSO4 adduct of 2,2′-dithiopyridine-1,1′-dioxide (MDS).
U.S. Pat. No. 4,370,325 discloses a composition containing 2,2′-dithiopyridine-1,1′-dioxide or one of its metal salt adducts, including MgSO4 (MDS) and Zn salts, for treating eye and ear irritation and inflammation.
U.S. Pat. No. 4,235,873 discloses a deodorant composition containing 2,2′-dithiopyridine-1,1′-dioxide or one of its metal salt adducts, including MgSO4 (MDS) and Zn salts.
British Patent GB 2 230 190 A discloses a preservative composition containing an isothiazolone and the ZnCl2 adduct of 2,2′-dithiopyridine-1,1′-dioxide. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
Japanese patent application 6-134227 discloses an antibacterial filter incorporating ZnO or ZnO and zinc pyrithione. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
Japanese patent application 7-118103 discloses an antimicrobial composition for coating stainless steel washing machine drums to prevent fouling of inner surfaces wherein ZnO is used as a carrier in a ZPT thermoplastic resin coating. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
A technical journal article discloses that the presence of 0.2% metallic copper or 0.2% metallic zinc was found to decrease the biocidal activity of sodium pyrithione in 12 different metalworking fluids (E. O. Bennet et al. (1982) Int. Biodeterioration Bull. 18[1]: 7-12).
Another technical journal article (M. M. Khattar & W. G. Salt, Journal of Antimicrobial Chemotherapy (1993) 175-177) discloses the enhancement on the activity of pyrithione against Klebsiella pnenmoniae bacteria. More specifically, FIG. 2(a) of the Khattar & Salt article describes a favorable enhancement in the activity of 0.1% pyrithione against that bacteria that is attributable to the use of 0.01% of zinc chloride in combination with the pyrithione.
Copending patent application Ser. No. 09/599,371, filed on Jun. 22, 2000, discloses a biocidal composition comprising a combination of pyrithione, pyrithione salt, or pyrithione adduct, and a zinc or copper source, such as copper and/or zinc metal, oxide, hydroxide, or salt thereof. However, the antimicrobial compositions disclosed in this patent application will readily form insoluble precipitates as the concentrations of pyrithione and the zinc source are increased in the compositions, such as would be required to construct a concentrated biocidal composition (or “composition concentrate”). For example, compositions of pyrithione and zinc with concentrations greater than 0.0005% pyrithione and 0.00001% zinc will tend to form insoluble precipitates. These insoluble precipitates reduce the effectiveness of the composition as an antimicrobial agent, present problems for the long-term storage of a commercial product, and prohibit use where soluble biocides are required. Furthermore, the inability heretofore to construct a soluble, concentrated, biocidal composition of pyrithione and a zinc source necessitates the costly and inefficient administration of these components individually to applications, rather than in combination.
In addition, several patents have discussed solubilization of pyrithione derivatives with certain organic compounds.
U.S. Pat. No. 3,636,213 discloses solubilization of heavy metal salts of pyrithione (e.g., zinc pyrithione, copper pyrithione, and the like) using primary amines or polyalkyleneimines. However, this patent does not disclose any enhanced anti-microbial or anti-biofilm effect of the resulting solubilized pyrithione salts as compared to pyrithiones alone.
U.S. Pat. No. 3,940,482 discloses solubilization of heavy metal salts of pyrithione using long-chain polyamines for use in personal care products, such as soaps, shampoos, hairdressings, and the like. However, like the above patent, this patent does not disclose any improved or enhanced anti-microbial or anti-biofilm effect of the resulting solubilized pyrithione salts as compared to pyrithiones alone.
U.S. Pat. No. 4,835,149 discloses a method of solubilizing insoluble metal salts of pyrithione (such as zinc pyrithione, copper pyrithione, and the like) in the presence of certain amine compounds and certain aminocarboxylic acids. However, like the above patents, this patent does not disclose any improved or enhanced anti-microbial or anti-biofilm effect of the resulting solubilized pyrithione salts as compared to pyrithiones alone.
U.S. Pat. No. 5,114,984 discloses a process for imparting anti-bacterial and anti-fungal properties to a polyurethane foam by dissolving a pyrithione salt in an alkanolamine which is miscible in a polyol. However, like the above patents, this patent does not disclose any improved or enhanced anti-microbial or anti-biofilm effect of the resulting solubilized pyrithione salts as compared to pyrithiones alone.
Accordingly, what is needed in the art is a stable, soluble, concentrated biocidal composition of pyrithione, pyrithione salt, or pyrithione adduct, and a zinc source which permits the concurrent deliverance of high concentrations of pyrithione and zinc ions to an application, and which also offers an enhanced biocidal efficacy to pyrithione and its derivatives against free-living microorganisms and biofilms. Such a composition concentrate would be broadly useful, highly efficacious, cost-effective, and possess an enhanced biocidal effect both as an “in can” preservative and when diluted to form a “masterbatch” for use in a functional fluid, or when diluted directly into a functional fluid. The present invention is believed to be an answer to that need.